(1) Field of the Invention
The present invention relates to a process for producing hyaluronic acid matrix, more particularly, to produce hyaluronic acid matrix by decellularizing the tissue to provide a hyaluronic acid rich acellularization matrix.
(2) Description of the Prior Art
Hyaluronic acid (HA) is a glycosaminoglycan consisting of repeating disaccharides of alternating D-glucuronic acid and N-acetylglucosamine molecules. It is a straight-chained polymer with a molecular weight that varies between 50,000 and 13,000,000 Da.
Hyaluronic acid is naturally present in the pericellular gels, in the fundamental substance of connective tissue and in vertebrate organisms, of which it is one of the chief components, in the synovial fluid of joints, in the vitreous humor, in the human umbilical cord tissues and in rooster combs.
Hyaluronic acid plays a vital role in many biological processes. For example, hyaluronic acid is applied in the tissue repair process, especially in the early stages of granulation, stabilizing the coagulation matrix and controlling its degradation, favoring the recruitment of inflammatory cells such as polymorphonucleate leukocytes, and orientating the successful migration of epithelial cells.
Besides, the application of hyaluronic acid solutions could accelerate healing in patients suffering from sores, wounds and burns. It is also known that hyaluronic acid fractions can be used to facilitate tissue repair, as substitutes for the intraocular fluid, or they can be administered by the intra-articular route to treat joint pathologies.
Because of different producing processes, there are two kinds of hyaluronic acid, one is the isolation-origin HA and the other is the fermentation-origin HA.
The process to produce the isolation-origin HA includes removal of epithelium from the rooster comb, grinding of rooster comb, treatments in acetone and multiple treatments with ethanol and sodium chloride solutions. The process to produce the fermentation-origin HA is by continuous fermentation of Streptococcus in a chemostat culture.
The fermentation-origin HA typically includes significant levels of endotoxins and higher levels of bacteria that must be removed. Therefore, it needs to be more purified in order to eliminate as many bacterial proteins as possible. It is to say that the problem of traditional batch culture in which degradation enzymes can begin to break down the cell walls of Streptococcus is releasing cell contents into the fermenter broth, leading to purification difficulties.
The isolation-origin HA as produced in biological systems, is associated with proteins and other glycosaminoglycans, so it has to be extensively purified. The complex purification procedures are required in order to obtain a pure product from the sources mentioned above, especially rooster combs, without too much degradation of the molecular chains. Even if very sophisticaed methods for purification and sterilization, have been developed it is inevitable that the molecular weight decreases during these steps and the final product in most cases has much lower molecular weight.
In other words, one important issue of producing isolation-origin HA with this material is the likelihood of it being contaminated by viruses. Complex purification procedures are therefore needed. However, the complex procedures will cost a lot.